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Toxiderma

Medical expert of the article

Dermatologist, oncodermatologist
, medical expert
Last reviewed: 04.07.2025

Toxicoderma (toxicoderma) is a general toxic-allergic disease with predominant manifestations on the skin and mucous membranes, arising as a result of hematogenous spread of chemical (medicinal, less often protein allergens) that have entered the body by ingestion or parenteral administration, by inhalation or by massive resorption through the skin and mucous membrane.

The term "toxicoderma" was first introduced by G Yadasson (18%), who noted the predominantly medicinal origin of this disease. Many authors, both domestic and foreign, consider medicinal toxicoderma to be the most common manifestation of drug disease.

Causes toxiderma

The main factors in the etiology of toxicoderma are:

  • medications (antibiotics, sulfonamides, analgesics, barbiturates, B vitamins, novocaine, furacilin, rivanol, etc.);
  • chemicals (chromium, nickel, cobalt, molybdenum, arsenic, mercury, etc.);
  • food products (preservatives, exotic fruits, eggs, chocolate, coffee, mushrooms, fish, nuts, etc.).

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Risk factors

Risk factors include: genetic predisposition, neuroendocrine disorders, diseases of the digestive system, dysbacteriosis, rapid breakdown of microbes that cause a specific endotoxic reaction.

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Pathogenesis

Side effects and complications of drug therapy can be divided by etiology into toxic-metabolic, allergic, infectious, neurogenic and those caused by discontinuation of medication.

Toxic-metabolic complications are usually associated with the chemical and pharmacological properties of the drug, its overdose, duration of use, cumulation, synergism. Toxic complications often have a specific character, typical for a certain drug or a group of drugs similar in chemical structure (mercury, arsenic, halogens).

Allergic reactions to chemical (medicinal) or protein substances are usually associated with individual hypersensitivity of the patient. Penetration of chemical or protein allergens into the body stimulates its defense with the help of the immune system. Immunological reactions that occur with damage to skin tissues in toxicodermia, by the nature of the course and the mechanism of development, are divided into reactions of immediate-type hypersensitivity (ITH) and delayed-type hypersensitivity (DTH) of the cytotoxic type of immune reaction.

The concentration of specific antibodies produced by immunocompetent cells (B-lymphocytes, plasma cells), the amount of fixed antibodies on mast cell membranes, and a certain ratio between antigens and fixed antibodies are important for triggering immediate-type allergic reactions. This is confirmed by the results of skin tests with penicillin and streptomycin.

An example of a drug reaction that develops exclusively or predominantly of the immediate type in the first hours after taking sulfonamide drugs, pyrazolone derivatives (amidopyrine, analgin) and barbituric acid (luminal, barbamil) is toxicoderma of the urticaria type, erythema multiforme exudative and fixed erythema.

Delayed-type allergic reactions are caused by cells, mainly T-lymphocytes and macrophages, as well as lymphokines (transfer factor) and hormones of the thymus gland.

During the development of DTH, repeated entry of an antigen (chemical substance, protein) into the body causes migration of sensitized lymphocytes to the area where there is an antigen fixed by skin proteins. As a result, reacting with the fixed antigen, sensitized lymphocytes secrete cellular mediators lymphokines, which have inflammatory and regulatory properties. Regulatory lymphokine (transfer factor) activates the functions of T- and B-cells. Inflammatory lymphokines include cytotoxins, with the help of which sensitized lymphocytes (specific T-effectors) directly participate in immune lysis of cells, as well as a humoral inflammatory factor that increases the permeability of capillary walls, which facilitates the migration of cells from the bloodstream to the area of allergic inflammation. Most often, a toxic-allergic reaction of the DTH type is manifested by spotty-papular and spotty-vesicular elements with a predominance of the hemorrhagic component.

The body's immune response to the ingestion of a chemical substance may involve damage to skin tissues by the T-cytotoxic reaction type, which is carried out by sensitized lymphocytes (T-effectors) together with macrophages that lyse cells. Cell destruction occurs through direct contact with aggressor cells and the release of cytotoxins by the latter - acid hydrolases. The cytotoxic effect is especially clearly seen in the pathogenesis of bullous toxicodermia and Lyell's syndrome, in which the leading pathomorphological sign is epidermolysis.

Damage to cells and intercellular structures as a result of toxic effects of medications or allergic reactions imparts an autoantigenic property to them, which causes the formation of autoantibodies. Under appropriate conditions, the complexes "autoantigen-autoantibody-immune complexes" enhance the process of damage to cells, organs, tissues, and vessels.

Autoallergic reactions play a significant role in the pathogenesis of drug reactions such as vasculitis, systemic lupus erythematosus, and eczema-like lesions.

In the development of some forms of toxicodermia, the damaging and sensitizing action of the skin microbial factor should be taken into account. The effect of bromine and iodine preparations on the skin, which change the chemistry of sebum, contributes to the activation of staphylococcal infection, which is included in the pathogenesis of such toxicodermia as bromoderma and iododerma.

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Symptoms toxiderma

Symptoms of toxicodermia are characterized more often by polymorphic, less often by monomorphic inflammatory rashes that appear against the background of a general deterioration in health.

Spotted-papular rashes are observed more often with the introduction of antibiotics (penicillin, streptomycin, olegetrin, griseofulvin, lamidil), analgesics, B vitamins, novocaine, rivanol, furacilin. Spots of an inflammatory nature, often hyperemic, ranging in size from pinpoint to confluent erythema, are usually located over the entire skin, often spreading from top to bottom or affecting mainly the skin of folds or areas experiencing additional physical stress.

The nodular rash associated with spots is usually disseminated, sometimes tends to focus and merge, and is usually represented by lymphoid papules of a round shape, bright pink color. As the disease progresses, usually on the 4th-5th day, peeling appears on the surface of the spots and papules, most often in the form of delicate translucent scales, covering the entire surface of the rash elements.

Under the influence of effective therapy, the rash resolves, leaving in rare cases unstable hemosiderin pigmentation.

Skin rashes are often accompanied by itching, fever up to 38 °C, general malaise, chills, headache. Moderate leukocytosis and eosinophilia are noted in the blood.

Fixed (sulfanilamide) erythema

In 1894, the French dermatologist L. Brocq first proposed the term "fixed rash". Currently, the synonym "fixed erythema" is used to denote drug-induced spotty-plaque, spotty-urticarial or vesicular rashes that recur in the same areas and leave behind persistent pigmentation.

In the vast majority of patients, the cause of this type of toxicoderma is the use of sulfonamides, less often other medications (barbiturates, analgesics, antipyretics).

Skin lesions with fixed erythema are characterized by the appearance of single lesions at first, and then multiple lesions. The primary lesion is most often localized on the mucous membrane of the mouth, trunk, in folds, on the back of the hands, on the feet, on the genitals.

At first, one or more spots appear, 2-5 cm in size, brownish-blue or with a lilac tint, with the peripheral zone being brighter than the central one. The spot is round in shape, sharply demarcated from healthy skin. Later, the center of the spot slightly sinks, acquiring a grayish tint, or from the center to the periphery, the rash begins to regress and its color becomes brown, the elements acquire the shape of semicircles, ruts and garlands. Sometimes a blister may form in the center of the spotted elements.

The rash is accompanied by itching and burning. The elements on the skin exist for up to 3 weeks. In the widespread form of fixed erythema, an increase in body temperature, muscle and joint pain are observed. In the acute period of the disease, leukocytosis, eosinophilia and increased ESR are observed in the blood.

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Toxicoderma of the urticaria type

Urticaria is a common reaction to various medications: penicillin, tetracycline, erythromycin, analgesics, trichopolum, novocaine, lidase, etc. The rash appears in the first days of taking the drug and is characterized by the appearance of blisters on the skin and severe itching. The size of urticarial rashes varies from a lentil to a palm, the borders of the elements are clear, the consistency is dense and elastic (doughy), the shape is round or bizarre. Urticarial dermographism is often noted. The color of the elements ranges from bright red to pearly white.

As a rule, urticarial rash is abundant, covering the entire skin of the face, trunk and limbs. In severe cases, the process is accompanied by swelling of the mucous membranes of the mouth and larynx, turning into Quincke's edema.

With generalization of the skin process, general weakness, malaise, headache, rise in body temperature to 38-38.5 °C, arthralgia and myalgia are possible. A persistent increase in the number of eosinophils is observed in the blood.

Bromoderma and Iododerma

Relatively rare and difficult to diagnose are toxicodermas that occur as a result of taking bromide and iodine drugs - bromoderma and iododerma.

Bromoderma is characterized by various types of rashes: erythematous, urticarial, papulopustular, vesicular, bullous, warty and acne-like.

Acne bromide, which is the most common and typical form of bromoderma, appears as pinhead- to lentil-sized follicular pustules and abundant pinkish-purple nodular lesions on the face, back, and extremities. After healing, small superficial scars of a brownish-purple color may remain.

Tuberous bromoderma (vegetative) occurs more often in young women. The rash looks like a few limited nodular and tumor-like plaques of violet-red color, rising above the skin by 0.5-1.5 cm. The size of the nodes is from a pea to a pigeon's egg, they are covered with bloody-purulent, fairly dense crusts. After removing the crusts, an ulcerous tuberous surface is exposed, on which warty-papillary growths can develop. When the lesion is squeezed, abundant pus is released on the vegetative surface. The entire "tumor" resembles a soft sponge soaked in pus. Visible mucous membranes are rarely affected. The disease proceeds favorably, leaving behind atrophic scars and pigmentation.

Iododerma most often manifests itself in bullous and tuberous forms. The tuberous form may be complicated by vegetations. In bullous iododerma, the rash usually begins with tense blisters from 1 to 5 cm in diameter, filled with hemorrhagic contents. After the blisters open, the bottom is exposed, covered with significant vegetations.

Tuberous iododerma begins with a nodule, which then turns into a pustule and a tumor-like formation up to 5 cm in size. The peripheral edge of the lesion is slightly elevated and consists of small bubbles with liquid serous-purulent contents. The consistency of the lesion is pasty, when pressing on the surface, pus with an admixture of blood is easily released. Most often, iododerma is localized on the face, less often - on the trunk and limbs.

Clinically, there is a great similarity between tuberous iododerma and bromoderma, associated with the same mechanism of occurrence as a result of taking drugs belonging to the same chemical group.

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Lyell's syndrome

The first description of toxic epidermal necrolysis was made by the English doctor A. Lyell in 1956 based on the clinical observation of 4 patients. In 1967, he published his observations of 128 cases of this disease, having analyzed his own results and the data of other English doctors. Until now, this syndrome has been called differently in the literature: polymorphic necrotic epidermolysis: "scalded skin" syndrome; scald-like necrotic epidermolysis; toxic-allergic epidermal necrolysis

A. Lyell characterizes the syndrome as a polyetiological disease, in the development of which, depending on the leading cause, 4 etiological groups can be distinguished:

  • Group 1 - allergic reaction to an infectious, mainly staphylococcal, process, most often observed in childhood;
  • Group 2 - the most common allergic reaction during drug treatment;
  • 3rd group - idiopathic with an unclear cause of development;
  • Group 4 - develops most often as a result of a combination of an infectious process with drug therapy against the background of altered immunological reactivity, with the direct participation of allergic mechanisms.

According to most authors, Lyell's syndrome develops as a non-specific reaction to the effects of drugs taken for various diseases. Most often, this disease is provoked by the intake of sulfonamides, antibiotics and antipyretics, derivatives of barbituric acid by patients.

It should be noted that the high frequency of occurrence of Lyell's syndrome is caused by the simultaneous use of prolonged-release sulfonamide drugs, antibiotics and antipyretics, among which aspirin, analgin and amidopyrine are especially frequently used.

Medicines taken for various diseases (ARI, pneumonia, exacerbation of chronic tonsillitis, diseases of the cardiovascular system, kidneys, etc.) can have an allergic effect.

In studying the pathogenesis of Lyell's syndrome, a number of authors give preference to the allergic theory. Evidence of this assumption is the presence in the anamnesis of various allergic diseases (allergic dermatitis, pollinosis, hay fever, bronchial asthma, urticaria, etc.) in the overwhelming majority of patients examined by them. The patients were found to have increased fibrinolytic activity and an increase in blood clotting time, which confirms the leading role of vascular lesions in the development of Lyell's syndrome. Immunofluorescence did not reveal antinuclear and antimitochondrial antibodies in the epidermis, and no changes in the content of immunoglobulins in the blood were established. These data made it possible to confirm that Lyell's syndrome cannot be interpreted as an immunodeficiency phenomenon - it is based on acute cell damage caused by the release of lysosomal structures.

The development of Lyell's syndrome, regardless of the causes that caused this disease, begins suddenly, accompanied by a rise in body temperature to 38-40 ° C, a sharp deterioration in health, weakness, often headache and arthralgia. Skin manifestations appear on the 2nd-3rd day, most often in the form of erythematous spots with pronounced edema, reminiscent of rashes with polymorphic erythema. Then quickly, within 24 hours, a hemorrhagic component joins, which usually occurs in the central part of the element, giving the erythema along with the growing periphery an "iris"-type contour. Gradually, the central zone of the elements acquires a grayish-ash color - exfoliation of the epidermis occurs.

According to some authors, the only reliable objective criterion for diagnosing Lyell's syndrome is epidermal necrolysis. The latter is confirmed by typical symptoms: in the lesions and outside them, in areas of "healthy" skin, the epidermis peels off spontaneously and at the slightest touch (the "wet linen" symptom) is rejected with the formation of extensive, extremely painful erosive surfaces that secrete abundant serous or serous-hemorrhagic exudate.

As the process progresses, blisters filled with serous contents continue to appear, rapidly increasing in volume and size with the slightest pressure on their surface and even when the patient changes position. Nikolsky's symptom is sharply positive (marginal and on outwardly unchanged areas). Pain of the entire skin is noted when touched. Simultaneously with skin manifestations, the red border of the lips, mucous membranes of the oral and nasal cavities, and genitals may be involved in the process. Mucous membranes of the eyes are often affected, which can lead to corneal opacity and decreased visual acuity, atony of the lacrimal canals, and hypersecretion of the lacrimal glands.

Of the skin appendages, nails are particularly often affected, and hair is less often affected. In severe cases of Lyell's syndrome, rejection of the nail plates may be observed.

Extensive erosive surfaces on the skin and mucous membranes secrete abundant serous or serous-hemorrhagic exudate, drying up in some areas with the formation of crusts. In the case of a secondary infection, the nature of the discharge becomes purulent, a specific smell of "rotting protein" occurs. The forced position of the patient due to the sharp pain of the skin and erosive surfaces often leads to the occurrence of ulcers mainly in places of pressure - in the area of the shoulder blades, elbow joints, sacrum and heels. A feature of these ulcers is sluggish healing.

The damage to the oral mucosa is accompanied by salivation, due to severe pain, swallowing and eating are difficult. Erosion of the urethral mucosa leads to urination problems.

In patients with Lyell's syndrome, damage to internal organs is possible (hypostatic pneumonia, toxic-allergic myocarditis, dehydration, hemorrhagic glomerulonephritis, anuria, activation of focal infection foci) against the background of a sharp decrease in the body's defenses.

Stages

Depending on the severity of the course, mild, moderate and severe toxicoderma are distinguished. Mild lesions (grade I) include skin itching, moderate urticaria, fixed erythema with single foci, maculopapular form of exudative erythema, limited forms represented by papular rashes of the lichen planus type. The general condition of the patient does not change or changes insignificantly. Eosinophilia may be observed in the blood.

Moderate toxicodermia (grade II) includes urticaria with a large number of blisters, Quincke's stack, widespread rashes of erythematous-spotted, erythematous, papulovesicular and bullous nature, hemorrhagic vasculitis of the simple, rheumatoid or abdominal purpura type. At this stage of the disease, an increase in body temperature, changes in the blood, and sometimes damage to internal organs are noted.

Severe lesions (grade III) include Lyell's syndrome, Stevens-Johnson syndrome, erythroderma, nodular necrotizing vasculitis, iododerma, bromoderma, and other drug-allergic rashes combined with anaphylactic shock, serum sickness symptom complex, systemic lupus erythematosus, and nodular periarteritis.

Severe forms of toxicodermia are usually accompanied by damage to internal organs and can lead to death of the patient, especially with late diagnosis and inadequate therapy. The most common are maculopapular, maculo-urticarial rashes, less often bullous, vesicular and pustular forms of toxicodermia.

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Diagnostics toxiderma

In the blood of patients, there is initially moderate, then significantly increasing leukocytosis (8.0-10.0-10 9 /l), neutrophils shift to the left, an increase in the number of band neutrophils to 40-50%. In particularly severe forms of this disease, agranulocytosis or pancytopenia may develop. Biochemical changes in the blood are expressed in a decrease in the content of potassium and calcium, hypoproteinemia. Moderate hematuria, pyuria are determined in the urine, hyaline, waxy and granular cylinders appear - the result of damage to the renal tubular system.

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What do need to examine?

Treatment toxiderma

The lightning-fast progression of the disease, leading to total damage to the skin, a sharp deterioration in the general condition require immediate emergency therapeutic measures. The basis of specialized and combined therapy are corticosteroid hormones (prednisolone, dexamethasone, triamcinolone), which are prescribed in the first days of the disease in a dose of 250 to 300 mg, depending on the severity of the process and the extent of the lesion. Attempts to treat patients without the use of corticosteroids or with the use of small vines usually ended in death.

Recently, in the case of Lyell's syndrome, along with the usual hyposensitizing therapy (antihistamines, calcium preparations, ascorbic acid), hemodesis has been used.

Massive therapy with corticosteroid hormones, extensive wound surfaces that are the “entry gate” for purulent infection, the development of hypostatic pneumonia, and the activation of focal infection foci force the inclusion of cephalosporin antibiotics in the therapy at a daily dose of 4-6 g.

External therapy and careful care of the skin and mucous membranes play a huge role in the treatment of patients with Lyell's syndrome. The use of keratoplastic emulsions, ointments with the addition of antimicrobial agents in combination with sea buckthorn oil, rose hips, retinol acetate, daily dressings, treatment of erosive and ulcerative surfaces with solutions of aniline dyes serve as an effective means of restoring damaged skin and mucous membranes.

In terms of prognosis, timely hospitalization of the patient and early diagnosis of the disease are of great importance in Lyell's syndrome.

Thus, in the treatment of any form of toxicoderma, the main ones are:

  • discontinuation of the drug that caused Lyell's syndrome;
  • use of cleansing enemas, diuretics;
  • hyposensitization therapy - calcium preparations, antihistamines (suprastin, tavegil, diazolin, etc.):
  • detoxification therapy (hemodesis, sorbitol, etc.):
  • administration of corticosteroid hormones in severe cases.


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